An Empirical Model of Optimal Capital Structure

The authors provide a reasonably user-friendly and intuitive model for arriving at a company\u27s optimal, or value-maximizing, leverage ratio that is based on the estimation of company-specific cost and benefit functions for debt financing. The benefit functions are downward-sloping, reflecting the drop in the incremental value of debt with increases in the amount used. The cost functions are upward-sloping, reflecting the increase in costs associated with increases in leverage. The cost functions vary among companies in ways that reflect differences in corporate characteristics such as size, profitability, dividend policy, book-to-market ratio, and asset collateral and redeployability. The authors use these cost and benefit functions to produce an estimate of a company\u27s optimal amount of debt. Just as equilibrium in economics textbooks occurs where supply equals demand, optimal capital structure occurs at the point where the marginal benefit of debt equals the marginal cost. The article illustrates optimal debt choices for companies such as Barnes & Noble, Coca-Cola, Six Flags, and Performance Food Group. The authors also estimate the net benefit of debt usage (in terms of the increase in firm or enterprise value) for companies that are optimally levered, as well as the net cost of being underleveraged for companies with too little debt, and the cost of overleveraging for companies with too much. One critical insight of the model is that the costs associated with overleveraging appear to be significantly higher, at least for some companies, than the costs of being underleveraged

The Cost of Debt

We use exogenous variation in tax benefit functions to estimate firm-specific cost of debt functions that are conditional on company characteristics such as collateral, size, and book-to-market. By integrating the area between the benefit and cost functions, we estimate that the equilibrium net benefit of debt is 3.5% of asset value, resulting from an estimated gross benefit (cost) of debt equal to 10.4% (6.9%) of asset value. We find that the cost of being overlevered is asymmetrically higher than the cost of being underlevered and that expected default costs constitute only half of the total ex ante costs of debt

Religious innovation in modern African society: introduction

Brief elucidation of the diverse contributions to a special issue of "African Perspectives" concerning religious innovation in modern African society. RefASC – Publicaties niet-programma gebonde

The effect of rare alleles on estimated genomic relationships from whole genome sequence data

Relationships between individuals and inbreeding coefficients are commonly used for breeding decisions, but may be affected by the type of data used for their estimation. The proportion of variants with low Minor Allele Frequency (MAF) is larger in whole genome sequence (WGS) data compared to Single Nucleotide Polymorphism (SNP) chips. Therefore, WGS data provide true relationships between individuals and may influence breeding decisions and prioritisation for conservation of genetic diversity in livestock. This study identifies differences between relationships and inbreeding coefficients estimated using pedigree, SNP or WGS data for 118 Holstein bulls from the 1000 Bull genomes project. To determine the impact of rare alleles on the estimates we compared three scenarios of MAF restrictions: variants with a MAF higher than 5%, variants with a MAF higher than 1% and variants with a MAF between 1% and 5%. Results We observed significant differences between estimated relationships and, although less significantly, inbreeding coefficients from pedigree, SNP or WGS data, and between MAF restriction scenarios. Computed correlations between pedigree and genomic relationships, within groups with similar relationships, ranged from negative to moderate for both estimated relationships and inbreeding coefficients, but were high between estimates from SNP and WGS (0.49 to 0.99). Estimated relationships from genomic information exhibited higher variation than from pedigree. Inbreeding coefficients analysis showed that more complete pedigree records lead to higher correlation between inbreeding coefficients from pedigree and genomic data. Finally, estimates and correlations between additive genetic (A) and genomic (G) relationship matrices were lower, and variances of the relationships were larger when accounting for allele frequencies than without accounting for allele frequencies. Conclusions Using pedigree data or genomic information, and including or excluding variants with a MAF below 5% showed significant differences in relationship and inbreeding coefficient estimates. Estimated relationships and inbreeding coefficients are the basis for selection decisions. Therefore, it can be expected that using WGS instead of SNP can affect selection decision. Inclusion of rare variants will give access to the variation they carry, which is of interest for conservation of genetic diversity

Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring

Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. © 2015 The American Society of Human Genetics

Accuracy of imputation to whole-genome sequence data in Holstein Friesian cattle

Background The use of whole-genome sequence data can lead to higher accuracy in genome-wide association studies and genomic predictions. However, to benefit from whole-genome sequence data, a large dataset of sequenced individuals is needed. Imputation from SNP panels, such as the Illumina BovineSNP50 BeadChip and Illumina BovineHD BeadChip, to whole-genome sequence data is an attractive and less expensive approach to obtain whole-genome sequence genotypes for a large number of individuals than sequencing all individuals. Our objective was to investigate accuracy of imputation from lower density SNP panels to whole-genome sequence data in a typical dataset for cattle. Methods Whole-genome sequence data of chromosome 1 (1737 471 SNPs) for 114 Holstein Friesian bulls were used. Beagle software was used for imputation from the BovineSNP50 (3132 SNPs) and BovineHD (40 492 SNPs) beadchips. Accuracy was calculated as the correlation between observed and imputed genotypes and assessed by five-fold cross-validation. Three scenarios S40, S60 and S80 with respectively 40%, 60%, and 80% of the individuals as reference individuals were investigated. Results Mean accuracies of imputation per SNP from the BovineHD panel to sequence data and from the BovineSNP50 panel to sequence data for scenarios S40 and S80 ranged from 0.77 to 0.83 and from 0.37 to 0.46, respectively. Stepwise imputation from the BovineSNP50 to BovineHD panel and then to sequence data for scenario S40 improved accuracy per SNP to 0.65 but it varied considerably between SNPs. Conclusions Accuracy of imputation to whole-genome sequence data was generally high for imputation from the BovineHD beadchip, but was low from the BovineSNP50 beadchip. Stepwise imputation from the BovineSNP50 to the BovineHD beadchip and then to sequence data substantially improved accuracy of imputation. SNPs with a low minor allele frequency were more difficult to impute correctly and the reliability of imputation varied more. Linkage disequilibrium between an imputed SNP and the SNP on the lower density panel, minor allele frequency of the imputed SNP and size of the reference group affected imputation reliability

Genomic Prediction with 12.5 Million SNPs for 5503 Holstein Friesian Bulls

This study reports the first preliminary results of genomic prediction with whole-genome sequence data (12,590,056 SNPs) for 5503 bulls with accurate phenotypes. Two methods were compared: genome-enabled best linear unbiased prediction (GBLUP) and a Bayesian approach (BSSVS). Results were compared with results using BovineHD genotypes (631,428 SNPs). Results were reported for somatic cell score, interval between first and last insemination, and protein yield. For all traits, and both methods genomic prediction with sequence data showed similar results compared to BovineHD and GBLUP showed similar results compared to BSSVS. However, it remains to be seen if reliability of BSSVS with sequence data will improve after more sampling cycles have been finished

Genotype imputation accuracy in Holstein Friesian cattle in case of whole-genome sequence data

The use of whole-genome sequence data can lead to more accurate genomic predictions in animal and plants. Despite the fact that costs of sequencing are falling, sequencing a high number of individuals is still far too expensive. A promising approach is to sequence the genomes of a core set of individuals and impute the missing genotypes for the remaining individuals that are genotyped with currently available marker arrays. Relevant questions are how many animals do we need to sequence and what SNP arrays can we impute from for accurate imputation? Sequence data of 124 Holstein Friesian bulls from different countries were provided by the 1000 bull genomes project consortium (www.1000bullgenomes.com). Two chromosomes with distinct sizes (1 and 29) were selected for this study. The Beagle software was used for imputation and accuracy was assessed via cross validation. The 124 bulls were randomly divided into five sets: four sets were merged into a reference set (n_ref=100), and the remaining set in turn as the validation set. For the validation individuals all markers were set to missing, except for markers that occur on two commonly used arrays that include 777k and 54k SNP across the genome. In a second scenario the same was done, except half of the reference individuals were randomly removed (n_ref=50). Accuracy of imputation was calculated by the correlation between true and imputed genotypes per locus. The results will be presented and the impact of the size of the reference set and the marker density will be discussed

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs